Feline immunodeficiency virus (FIV) is a lentivirus that is associated with an immunodeficiency syndrome in naturally infected domestic cats. FIV was originally isolated from a feline leukemia virus (FeLV) negative cat at the University of California; this isolate designated FIV-Petaluma has become the prototype strain of FIV and was the original strain studied in this laboratory. A small animal model such as FIV infection of cats would be highly valuable as a model for the testing of antivirals and vaccine strategies. Therefore, our goals were to develop FIV infection of the cat as an experimental model for the study of lentiviral pathogenesis and AIDS. The specific objectives of this study were: (1) the molecular and biochemical characterization of FIV-Petaluma, (2) the infection of specific pathogen-free or domestic cats with FIV and a detailed analysis of the clinical response of infected cats, (3) an analysis of the genetic diversity of FIV isolates, (4) the development of reagents for vaccine trials, and (5) the search for FIV-related lentiviruses in wild cats. The major goals of this project in the past year have been the molecular characterization of a lentivirus isolated from Florida panthers, a wild cat that inhabits the Florida Everglades. The entire sequence of this panther lentivirus (PLV) was derived from PCR generated clones that span the genome. PLV is distantly related to FIV from domestic cats and shares a similar genome structure. The relationship between PLV and FIV is similar to that observed for different subgroups of the primate lentiviruses; the regulatory genes are poorly conserved, whereas the gag and pol proteins share 52 and 60% amino acid identity, respectively.